MALE FACTOR SUBFERTILITY
.(slide show by Prof. S K Pal-Kolkata)
,
Prevalence:-
Males are entirely responsible
for subfertility in 1/3 rd of all
subfertility problem, and is partly responsible for another 20% cases. In total about 50% of all cases of
subfertility males are involved.
Normal
Seminal Parameters:- WHO Lab
Manual(2010)- in App. A1.1 declares of all fertile men(whose partners were able to conceive by 12 months of trying):- in
5% of such fertile men the seminal criteria
were Density = 15 million/ ml; 32% for good forward progression ( motility within 60 minutes of ejaculation,
and normal morphology of 4% . Such apparently suboptimal seminal
parameters which will readily prompt us to jump for antioxidant therapy will
refrain us from doing so after promulgation of W H O Manual. This study of WHO
will offer an anxiety free life to the
couple for at least first few yrs of trying
if they are young and the concerned man , according to WHO can’t be just
called be infertile ,albeit may be
called as substandard semen sample.
What are the common causes of male
subfertility?
In about 50%
of cases of male subfertility no obvious cause is detected. Possibly monogenic
disorder .There is no watertight separation between different causes of which
contributes to male subfertility. Thereby I mean many minor abnormality may
lead to 1) OAT(oligozoospermia . 2) asthenozoospermia, Teratozoospermia ) .
However =
Nonobstructive azoospermia 30%; Idiopathic (no obvious cause-)-25%; testicular
failure 9%, seminal disodreds-7%, Obstructive azoospermia-6%;
Cryptorchidism-6%., MAGI(Male Accessory Gland Infections)
Basically there are three types of diseases which can be clinically
diagnosed. Such are A) complete absence of sperms in the ejaculated semen-azoospermia
B) Sperms are present but their quality or quantity is far less to yield
fertilization and to develop embryonic competency and successful pregnancy. C)
The third group is that male sexual disorders where the male partner is unable
to deposit semen at the right time of fertile period.
Type 1 Male Infertility:: -Absence of sperms (Azoospermia):- 1) Primary Testicular Failure-this occurs during intra
uterine life i.e. development process. In such cases FSH will be high. This is
the most common cause of azoospermia. One
subtype of this is a syndrome called TDS=Testicular Dysgenesis
Syndrome- which lead to low or absent sperms. Cryptorchidism, Hypospadias
are other rare causes -.Therefore pregnant mothers should maintain optimal health so that the
foetus inside womb grow properly.
2) Genetic diseases
so that sperm production is interfered . In fact this is the most common cause of azoospermia) 3) Idiopathic
(cause not known inspite of several investigations), 4) Hypothalamic-Pituitary Diseases
(Primary hypogonadism). Additionally, following diseases can lead to
absence production of sperms in the testis e.g. Testicular Dysfunction
Syndrome, Maldescent of testis, Torsion of testis, Viral and bacterial
infections, Chemotherapy and radiation.
Testicular Dysfunction
Syndrome (not to be confused with the previously described Testicular
Dysgenesis Syndrome- . This syndrome is the result of variety of factors which
are in operational. Many uphold the view that there is point
mutations but environment has an added
role in the expression of the disease e.g. maternal toxins, maternal life
style, dietary habits, lack of exercise . However, in continuation with point
mutation paracrine theory in
cases of TDS is also contribute to nonproduction of sperms . This absence of
local coordination between different growth factors and paracrine funaction
eventauly lead to stoppge of spwrm function .
Therefore there
is both abnormal functions of Leydig cells (which secrete intratesticular androgen)
and abnormal secretions / synthesis of Sertoli cells . Sertoli cells are the
PILLARS of a multi storied bldg and normally secrete many known & unknown products which pass on t nearby semimeferous tubules to synchronize the
production and some degree of maturation(acquision of functional competency of
sperms) spermatogenesis. But final
maturation of sperms occurs at epididymis.
Type
2 Few points on oligoastheno zoospermia (not azoospermia) : : Sperms
are present but are of poor quality:- The causes are 1) MAGI- Male
Accessory Gland Infections of varying nature, 2)Acquired Testicular damage(
sports injury-cricket ball injury in particular). ---A partial damage-à therefore subnormal functioning of
testis –
Sperm
production can also be interfered with-
Life style factors, Obesity, Environmental
toxins, Varicocele, systemic
disease, Ageing, Immunological causes, one sided obstruction of ejaculatory
duct (either vas or epididymis).
Type 3 Male
Subfertility. Male sexual
Disorders:- Disorders of Erection, Or ejaculation.
Mostly
psychological drugs, Psychotherapy,
Sildenafil types of drugs may work.
\. Is
there any seasonal variation of seminal quality?
Age-adjusted
analyses of seasonal variations in andrology patient semen parameters showed
significant seasonal variation in the percentage rapid motile sperm and straight-line
velocity, as well as the percent tail defects, percent immature sperm, and the percent
tapered sperm. Such seasonal variations might prove to be clinically relevant
and important when designing experimental protocols.
Clinical Examination:
tall, robust, less beard, scanty moustache- may be a case of Klinefelter’s Syndrome. Age above>
50 yrs= poor sperm quality.
What is Kartageners syndrome (KS) Association of primary ciliary dyskinesia along with
situs inversus is termed as Kartageners syndrome (KS). Though some scientists insist that only when triad of 1)
chronic sinusitis, 2)
bronchiectasis 3) situs inversus exist then and then only that
person will be labeled as KS. Dextrocardia and dysosmia as well as a history of
chronic bronchitis and sinusitis, the classic triad disorders Kartageners
syndrome ( KS)
What is Young Syndrome ?
The association of
frequent RTI, along with azoospermia is called Young Syndrome. The azoospermia is “Obstructive in nature “
and is due to inspissations of
secretions in the epididymis.
What is Cystic Fibrosis
disease ?
It is a common autosomal recessive disorder more
common in Northern part of Europe. CFTR
is important for maintenance of viscosity and fluidity of epithelial
secretions. If there are mutations of CFTR gene than CBAVD-or sinusitis. Vas is
often absent.
.
. History
of Male Partner.
Local infections, Trauma on testis, H/o
Mumps, Kochs, Filariasis, Viral diseases,
Polygamy, Local hygiene, . Testicular trauma, undescented testis,
History of sexual dysfunction, Stress of modern society and food habits. Loss
of libido and premature ejaculation.-warrant psychological support. Drug Intake/ Life style. How he spend his life ??
Degree of stress relaxation, sports, enjoying holidays, any fear losing job,
Occupational exposure to toxins, Alcohol, smoking, Cancer chemotherapy causes
some damage to germ cells- e.g. cyclophospamide. What is the total number of drugs currently he is
consuming ? More the number of drugs-à more probability of seminiferous
tubule damage. There will be chromosomal brakes and abnormal of springs.
History of
Male Partner :Sexual history:-
Any impotency, premature/ retrograde
ejaculation
H/O Surgery :- Scrotal surgeryàhernia, Hydrocele, Brain surgery,
Hernia repair, Retroperitoneal sympathectomy
History of
Male Partner : Any Medical diseases:/Sytemic Diseases.-
If there is recurrent Respiratory tract
Infections –then one should consider Cystic fibrosis gene mutations. In such
cases vas will be congenitally absent of vas
on either side also called CABV. There are two special symptoms associated with
either azoospermia or OAT. These are Kartageners Syndrome e.g. ciliary defects
and Young syndrome which mean the there is inspissations of testicular
secretions at the level of epididymal level.
History of Male Partner(contd)
Central
Nervous system Tumours—Thyroid diseases, Liver abnormalities are not uncommon
accompaniment of poor quality of sperm. Similarly visual fields problem and
headache will raise suspicion prolactin disorder. Hepatomegaly associated with
Gynaecomastia points to alcoholic liver diseases or other disorders of steroid
metabolism.
Following
points have to be enquired e.g.,
1) Pubertal
development:
3) Any
history of anosmia? Cannot smell properly.
4) Sexual
history- Change of libido, Erectile or ejaculatory disorders. Any psychiatric
drug therapy?
Clinical
Examination of Male Partner.
Gynaecomastia; Eunuchoid appearance,
less body hairs, absence of male pattern body hairs, Small testis. Any
hydrocele, hernia, epididymitis, any scar in scrotum/ inguinal region, Per rectum palpable seminal vesicles and or
enlarged prostate.
,
Investigations
of male partner (Contd)
A) Hepatitis
serology, B) Viral Screen c) Ebsocrine : TSH, Free T4, PRL ,testosterone
D) BMI
E) Rpt semen analysis . If earlier repot suggest suboptimum then one
should repeat preferably after 2 months i.e Routine semen analysis, F) Lab tets for for systemic diseases, G) . Sperm function tests, H) . Chromosomes.
Gene testing, I) Venography is not done nowadays but scrotal
sonography and imaging of seminal vesicles and Prostate should be done by
TRUS(Trans Rectal Ultrasonography) . His is warranted if repeated routine tests reveal poor seminal parameters.
.
Treatment
of Male Subfertility:--
Unlike
females the defects in males are difficult to ameliorate. Many therefore jump on to IUI procedure . However the recognized methods
of treatment (medical Treatment are A) Life style modifications, Hormones like
gonadotrophins, Antioxidants. Presence of ROS I seminal fluid is being
recognized fast /.
Role of Antioxidants and vitamins in male subfertility?
Many doctors do
prescribe 1)L- carnitine,2)
Astaxanthin,3) Vitamin E, 4)
Vitamin C, 5) Co-Q, 6) Zn, 7) Lycopene,
8) Selenium, 9) L-arginine, 10) Alpha- Calcidol, 11) Omega-3 Fatty acids, 12)
DHA and 13) F. Acid 14) Glutathione to
promote fertilizing potential of ejaculated sperms.. It is understandable that role of antioxidants in male subfertility is
somewhat effective as time and again has
been notices that the quantum of ROS in seminal
fluid is high when seminal parameters are substandard.
What
antioxidant in what dosage?
There are many
questions which remain unanswered. A) What element B) combination of elements
to Supplemt and at C) what dosage? D) How long? E) How do we select out of
eight commonly recognized antioxidants which one is will help one particular
person??Unfortunately, answer is not known to us. Admittedly many of us empirically
supplement antioxidants. For instance, in cases say 10th per centile
motility, as a solo abnormality or say a case of combined with 15th per centile
morphology-what antioxidant will be most suitable if no obvious cause is
detected and couple is too young for IUI /ART?
What are
the medical Treatment for OAT ??
A)
:- Antioxidants, Vitamins, Life style changes, Timing of coitus, Treatment
of systemic diseases(DM, Thyroid, Hypertension, Psychiatric disorders),
Occasionally Inj testosterone ,better still inj. HCG 2000 i.u. at the dose of weekly three time. But in that serum
testosterone have to be measured 3 monthly. Some use Gonadotrophins for development of small testis but it will
be prudent to combine HCG along with HMG
as it is the hCG which stimulate Leydig cells to promote intratesticular
production
Treatemnt for zoospermia:-
One has to diagnose the kind of azoospermia.
Is it Obstructive (FSH & LH are normal and possibly absence of Fructose in semen)
or azoospermia is due to NOA(nonobstructive
azoospermia). In cases of Obstructive
azoospermia ans is surgical reconstruction of the blocked segment of vas/
Seminal vesicle. But question is will reconstructive operation will restore Patency
and functional sperms will be available
at ejaculate? If not ICSI/TESE are the solutions., .
What is
the “Technequies.of Sperm retrieval (Surgical Sperm Retrieval).”??
A) From
Epididymis:- 1) by percutaneous route- called PESA: percutaneous epididymal
sperm aspiration
2) MESA:_ Microscopic Epididymal Sperm Aspiration :- The
aspirated material is later processed by
density gradient centrifugation
B) From
Testis:-TESE- 1) Testicular
Sperm Extraction, 2) TEFNA:- Testicular Fine needle Aspiration.
Treatment of Oligozoospermia.
What is to be doe is sperm count (Density) is
low ? :- Better two reports from two different
lab at an gap of say 2-3 weeks and again
2 months apart to confirm the abnormality.
Upto 15 millions –No treatement. If abnormal sperms are upto 86% NO WORRY, NO
TRETMENT. By medical treatment 5-10 times increase in sperm count is possible.
Abstinence is often the cause of failure
of IUI as more abstinence will yield
either dead sperms or aged sperms .But
if morphology is below 4% normal-> then better IVF/ICSI.
Brand names
of different antioxidants
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BRAND
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Company
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Co-q
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l-Carnitine
|
Vit e
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zinc
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selenium
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lycopene
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Astaxanthin
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Dose per day.
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Fertisure-M
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Spectra-Sun
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50
mg.
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-340mg.
|
-
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5 mg.
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2500mcg
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8mg.
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Carnisure-500
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Elder
|
-
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500mg.
|
-
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-
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-
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-
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-
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2 tab TDS(3Gm)
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CoQ Forte
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Sanofi
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120mg
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Z-Y Forte
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Indecheme
35/- per cap.
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Co Q only-100
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-
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=
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Supakem
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Alkem-1 cap per day-12/-
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Superoxide dismutase.
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Paternia
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Zudys Nutriva
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30
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440
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bd
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Qute
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Yash
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Co-Q
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L-C
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vit
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Zn
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sel
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Lyco,Asta
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Carnimed Plus
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Xfert-mf
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Akumentis.
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yes
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1 cap & 1 tab daily.
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Types of
antioxidants:-
a)
Ace
antioxidant:- Astaxanthin
b)
Repairing
antioxidant: Lycopene
c)
Bio-energetic
Antioxidant: Co Q-10
d)
Nurturing Antioxidant: L= Carnitine
e)
Immunomodulatory
Antioxidant: Zn.
f)
Antioxidant
Ig Tg Forte (500mg.) 1 Cap
BD: (Alchemist) Rs. 17/-, Colostrum Natural.
To determine the
expression and enzymatic activity of glutathione peroxidase (GPX)-1, GPX-4, and
glutathione reductase together with glutathione (GSH) concentrations in
spermatozoa from fertile and infertile men.
Design
Prospective study.
Setting
University-affiliated
private center.
Patient(s)
Fifty-four infertile
men undergoing assisted reproduction techniques and 55 fertile sperm donors
with pregnancies and newborns by artificial insemination.
Intervention(s)
None.
Main outcome measure(s)
Analysis of gene
expression by fluorescent quantitative polymerase chain reaction and an
analysis of enzymatic activity and GSH concentration by controlled biochemical
reactions and spectrophotometry.
Result(s)
GPX-4 activity but not
mRNA expression is directly related to sperm morphology (strict criteria) and
is more compromised with a low percentage of normal sperm. These differences
are also demonstrated when fertile and infertile men were compared. In
addition, intracellular GSH concentrations are lower when sperm morphology is
severely impaired, but no differences were found between fertile and infertile
men.
Conclusion(s)
Intracellular sperm
GSH system components GPX-4 and GSH are altered in infertile men, and these
alterations seem to be linked to sperm morphology
